Synthesis, anti‐proliferative activities, docking studies, and computational calculations of novel isonicotinic mixed complexes

Abstract

In this investigation, we studied the mixing of two ligands, isonicotinohydrazide (L1) and 3-hydroxyisonicotinic acid (L2), with different metal ions to afford the corresponding stable metal complexes. Consequently, intensive physico-chemical analysis including elemental analysis, UV–visible, Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA), mass, 1H nuclear magnetic resonance (NMR), X-ray diffraction (XRD), magnetic, and molar conductance measurements has been performed. The thermal stability of all complexes was determined using TGA, and the kinetic parameters were obtained using the Coats–Redfern method. Both the degree of crystallinity and the unit cell of all complexes were determined utilizing XRD studies. Furthermore, these metal complexes exhibited excellent anti-proliferative activity against human breast cancer (MCF-7) and human liver cancer (HepG2) cell lines against the doxorubicin drug. The Co(II) complex outperformed all other metal complexes in terms of activity, which was confirmed by molecular docking stimulation via the binding energy with amino acids in a structural complex of Kaposi's sarcoma-associated herpesvirus (KSHV) thymidylate synthase (PDBID:5H38) and the ternary complex of KRIT1 bound to both the Rap1 GTPase and the Heart of Glass (HEG1) cytoplasmic tail (PDBID:4hdq) and shortage. Moreover, these metal complexes were optimized via theoretical investigation through a density functional theory (DFT)/ B3LYP/LANL2DZ basis set to confirm the stability of these metals theoretically and detect frontier molecular orbitals (FMO), electrostatic potential (ESP), energy gap, and physical computational calculations. Eventually, the electrochemical features were explored using cyclic voltammetry (CV) and electrochemical impedance spectra (EIS).